ABSTRACT
BACKGROUND: Hydrogen is received as an inert gas that thought to be non-functional in vivo previously. Recently, emerging evidences showed that in ischemia/reperfusion (IR) condition, hydrogen reduced cellular reactive oxygen species (ROS) production and ameliorated cell apoptosis. However, the underlying mechanism of hydrogen on IR-induced apoptosis remains elusive. Here we tried to unravel the mode of action of hydrogen with rat adrenal medulla cell line PC-12 in vitro. METHODS: The mitochondrial functions before and after oxygen glucose deprivation and reperfusion (OGD/RP) were determined with corresponding dyes. The expression of Bcl-2, Bax, VDAC1, cytochrome c and caspase 9 was detected using qRT-PCR and Western Blotting method. Then Bcl-2 inhibitor, AB-199, was applied to investigate the role of Bcl-2 in OGD/RP-induced cell apoptosis. Finally, we manipulated the expression of VDAC1 with plasmids transfection to understand the effects of VDAC1 on Bcl-2-mediated anti-apoptosis in OGD/RP. RESULTS: In this study, we demonstrated that hydrogen-rich saline (HRS) reduced OGD/RP-mediated neuronal loss by stimulating the expression of Bcl-2, which suppressed the activity of VDAC1. Consequently, HRS maintained the mitochondrial functions, restrained the release of cytochrome c and caspase 9 activation, resulting in ameliorated cell viability. CONCLUSIONS: HRS ameliorated OGD/RP-induced PC-12 cell apoptosis and provided a novel treatment option for ischemia.
Subject(s)
Glucose/deficiency , Hydrogen/pharmacology , Hypoxia/drug therapy , Proto-Oncogene Proteins c-bcl-2/metabolism , Saline Solution/pharmacology , Voltage-Dependent Anion Channel 1/metabolism , Animals , Apoptosis/drug effects , Caspase 9/metabolism , Cell Death/drug effects , Cell Hypoxia/drug effects , Cell Survival/drug effects , Cytochromes c/metabolism , Glucose/metabolism , Hydrogen/chemistry , Hypoxia/metabolism , Membrane Potential, Mitochondrial/drug effects , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/pharmacology , Oxygen/metabolism , PC12 Cells , Rats , Reactive Oxygen Species/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Saline Solution/chemistry , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVE: To further evaluate the efficacy and safety of tribendimidine in treatment of adult patients with intestinal nematode infections. METHODS: An open and multi-center clinical trial was conducted in the provinces of Hainan, Sichuan and Guizhou. A total of 1,292 infected cases aged 15-70 years were enrolled in the study. Modified Kato-Katz method was used to diagnose the cases with intestinal nematode infections and assess the efficacy 3-4 weeks post treatment. Patients with Ascaris lumbricoides infection were treated orally with tribendimidine enteric coated tablets at a single dose of 300 mg, while in the patients with Ancylostoma duodenale, mixed A. duodenale and A. lumbricoides, or with other helminth infections, a single dose of 400 mg was administered. RESULTS: The cure rate and effective rate of the patients with Ancylostoma infection were 88.4% (1,009/1,141) and 99.1% (1,131/1,141), respectively, while in patients with A. lumbricoides infection, they were 95.0% (419/441) and 99.8% (440/441), respectively. The cure rate of tribendimidine enteric coated tablet given to patients with Trichuris trichiura infection at a single dose of 400 mg was 76.8% (109/142). The adverse effect induced by tribendimidine was light and transient with a rate of 3.3% (42/1,292). No apparent impact was seen on blood and urine routine examinations, hepatic and renal functions as well as ECG examination. CONCLUSION: It is further confirmed that under the used dosage for expanding treatment in larger sample of patients with various ages and infected with Ancylostoma duodenale, A. lumbricoides and other helminths, tribendimidine enteric coated tablet is safe with satisfactory efficacy.
Subject(s)
Intestinal Diseases, Parasitic/drug therapy , Nematode Infections/drug therapy , Phenylenediamines/therapeutic use , Adolescent , Adult , Aged , Animals , China , Humans , Male , Middle Aged , Nematode Infections/parasitology , Phenylenediamines/adverse effects , Rhabditida/drug effects , Tablets, Enteric-Coated , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of tribendimidine in treatment of children with hookworm and Ascaris lumbricoides infections. METHODS: An open and multi-center clinical trial was conducted in the provinces of Hainan, Sichuan and Guizhou. 899 children aged 4-14 years were enrolled in the study. Hookworm, A. lumbricoides or other helminth infections were diagnosed by improved Kato-Katz method. All the patients were treated orally with tribendimidine enteric coated tablet at a single dose of 200 mg. The efficacy was evaluated by stool examination 3-4 weeks post treatment. RESULTS: The cure rate and effective rate of the children with hookworm infection were 82.0% (433/528) and 99.2% (524/528), respectively, while in children with A. lumbricoides infection, they were 95.0% (576/639) and 99.8% (637/639), respectively. The efficacy of tribendimidine enteric coated tablet given to the children with Trichuris trichiura infection at a single dose of 200 mg was 36.8% (112/304). The adverse effect induced by tribendimidine, such as dizziness, nausea and vomiting, was light and transient with an adverse effect rate of 1.6% (14/899). No apparent impact was seen on the blood and urine routine examination, hepatic and renal function as well as ECG examination. Conclusion Tribendimidine given at a single dose of 200 mg exhibits lower adverse effect rate and potential efficacy in the treatment of children with hookworm and A. lumbricoides infections.
Subject(s)
Intestinal Diseases, Parasitic/drug therapy , Phenylenediamines/therapeutic use , Tablets, Enteric-Coated , Adolescent , Ascariasis/drug therapy , Child , Child, Preschool , China , Double-Blind Method , Female , Hookworm Infections/drug therapy , Humans , Male , Phenylenediamines/adverse effects , Treatment Outcome , Trichuriasis/drug therapyABSTRACT
OBJECTIVE: To establish a sensitive, simple to use and low noise nested/multiplex PCR for simultaneously detection of Plasmodium falciparum (Pf) and Plasmodium vivax (P.v). METHODS: The tag primer amplification technique, software Primer Premier 5.0, NCBI-BLAST web resources and the matrix test were used to optimize the nested/multiplex PCR for detection of P.f and P.v with filter paper blood samples taken from malaria patients diagnosed by microscopy, and the results of the optimized nested/multiplex PCR and microscopy were evaluated. RESULTS: The sensitivity of the optimized PCR, determined by the examination of imitative filter paper blood samples, was about 1-2 parasites / microl for P.f and 5-10 parasites / microl for P.v. Primer-dimer and other PCR noise were removed. When 71 field filter paper blood samples taken from microscopically diagnosed patients (24 P.f, 47 P.v) were examined, the concordance between the optimized PCR and microscopy was 875% for Pf and 100% for P.v. CONCLUSION: The nested/multiplex PCR optimized by tag primer amplification technique is simple, with low noise and being able to detect Pf and P.v simultaneously. It is more sensitive in detecting cases with low parasitaemia and more accurate in identifying Plasmodium species than microscopy.
